An efficient genetic transformation system and suitable promoters are essential prerequisites for gene expression studies and genetic engineering in streptomycetes.In this study,firstly,a genetic transformation system...An efficient genetic transformation system and suitable promoters are essential prerequisites for gene expression studies and genetic engineering in streptomycetes.In this study,firstly,a genetic transformation system based on intergeneric conjugation was developed in Streptomyces rimosus M527,a bacterial strain which exhibits strong antagonistic activity against a broad range of plant-pathogenic fungi.Some experimental parameters involved in this procedure were optimized,including the conjugative media,ratio of donor to recipient,heat shock temperature,and incubation time of mixed culture.Under the optimal conditions,a maximal conjugation frequency of 3.05^10-5 per recipie nt was obtai ned.Subseque ntly,based on the above developed and optimized tran sformati on system,the synthetic promoters SPL-21 and SPL-57,a native promoter potrB,and a constitutive promoter permE commonly used for gene expression in streptomycetes were selected and their activity was analyzed using gusA as a reporter gene in S.rimosus M527.Among the four tested promoters,SPL-21 exhibited the strongest expression activity and gave rise to a 2.2-fold increase in p-glucuronidase(GUS)activity compared with the control promoter permE.Promoter SPL-57 showed activity comparable to that of permE.Promoter potrB,which showed the lowest activity,showed a 50%decrease in GUS activity compared with the control permE.The transformation system developed in this study and the tested promotors provide a basis for the further modification of S.rimosus M527.展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
In this paper, we consider 2 × 2 non-cooperative elliptic system involving Laplace operator defined on bounded, continuous and strictly Lipschitz domain of Rn. First we prove the existence and uniqueness for the ...In this paper, we consider 2 × 2 non-cooperative elliptic system involving Laplace operator defined on bounded, continuous and strictly Lipschitz domain of Rn. First we prove the existence and uniqueness for the state of the system under conjugation conditions;then we discuss the existence of the optimal control of boundary type with Neumann conditions, and we find the set of equations and inequalities that characterize it.展开更多
The existence and uniqueness of the state for 2 × 2 Dirichlet cooperative elliptic systems under conjugation conditions are proved using Lax-Milgram lemma, then the boundary control for these systems is discussed...The existence and uniqueness of the state for 2 × 2 Dirichlet cooperative elliptic systems under conjugation conditions are proved using Lax-Milgram lemma, then the boundary control for these systems is discussed. The set of equations and inequalities that characterizes this boundary control is found by theory of Lions, Sergienko and Deineka. The problem for cooperative Neumann elliptic systems under conjugation conditions is also considered. Finally, the problem for n × n cooperative elliptic systems under conjugation conditions is established.展开更多
A comprehensive understanding of the relevance between molecular structure and passivation ability to screen efficient modifiers is essential for enhancing the performance of perovskite solar cells(PSCs).Here,three si...A comprehensive understanding of the relevance between molecular structure and passivation ability to screen efficient modifiers is essential for enhancing the performance of perovskite solar cells(PSCs).Here,three similarπ-πstacking molecules namely benzophenone(BPN),diphenyl sulfone(DPS),and diphenyl sulfoxide(DPSO)are used as back-interface modifiers in carbon-based CsPbBr_(3)PSCs.After investigation,the results demonstrate the positive effect of the p-πconjugation characteristic inπ-πstacking molecules on maximizing their passivation ability.The p-πco njugation of DPSO enables a higher coordinative activity of oxygen atom in its S=O group than that in 0=S=O group of DPS and C=O group of BPN,which gives a superior passivation effect of DPSO on defects of perovskite films.The modification of DPSO also significantly improves the p-type behavior of perovskite films and the back-interfacial energetics matching,inducing an increase of hole extraction and a decrease of energy loss.Finally,the unencapsulated carbon-based CsPbBr_(3)PSCs with DPSO achieve a maximum power conversion efficiency of 10.60%and outstanding long-term stability in high-temperature,high-humidity(85℃,85%relative humidity)air environment.This work provides insights into the influence of the structure ofπ-πstacking molecules on their ability to improve the perovskite films quality and therefore the PSCs performance.展开更多
Organic luminescent materials hold significant promise for applications in modern technology.Traditionally,their design has been guided byπ-conjugation theory.However,the recent discovery of weak interactions-based l...Organic luminescent materials hold significant promise for applications in modern technology.Traditionally,their design has been guided byπ-conjugation theory.However,the recent discovery of weak interactions-based luminescent materials,such as multiarylalkanes(MAAs),has challenged this paradigm.Emerging research suggests that these materials emit light from through-space conjugation(TSC),includingπ-π,n-π,and n-n TSC.Owing to their well-defined structures and facile chemical modification,MAAs serve as ideal models for investigating TSC.This review systematically examines the mechanisms of TSC in these systems from three key perspectives:conformational regulation,donor-acceptor(D-A)and n-electronic modulation.Studies on their photophysical processes reveal that conformational control and D-A electronic modulation predominantly influence emission throughπ-πTSC.In contrast,tuning the n-electron structure,particularly involving lone pair electrons on nitrogen atoms,introduces n-πand n-n TSC,enabling red-shifted emission and enhanced luminescence efficiency.By providing a comprehensive analysis of TSC in MAAs,this review refines the current understanding of TSC-based luminescence and offers valuable design principles for developing novel,highly efficient,weak interactions-based luminescent materials.展开更多
The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and...The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).展开更多
After the third prezygotic division during conjugation of Paramecium caudatum,migratory and stationary pronuclei are produced.The migratory pronuclei remain in the paroral region tightly against the conjugating bounda...After the third prezygotic division during conjugation of Paramecium caudatum,migratory and stationary pronuclei are produced.The migratory pronuclei remain in the paroral region tightly against the conjugating boundaries;while the stationary pronuclei are located beside the migratory pronuclei.To date,however,it is not clear what causes this close side-by-side localization between migratory and stationary pronuclei.In the current study,immunofluorescence staining with monoclonal antibody of anti-α tubulin indicated that ＂U＂ or ＂V＂ shaped spindles connected the migratory and stationary pronuclei during the third prezygotic division.This observation accounts for the close localization between these two types of pronuclei.展开更多
Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted thera...Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.展开更多
Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended...Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended conjugation is designed and synthesized,named NaPh-4PACz.Compared to Ph-4PACz,NaPh-4PACz exhibits a larger adsorption energy with the ITO substrate,enabling the formation of a more uniform and dense film,thereby preventing direct contact between the perovskite and ITO.Additionally,NaPh-4PACz also has a stronger interaction with the perovskite,which can reduce buried interface defects and suppress non-radiative recombination.Consequently,NaPh-4PACz-based devices achieved a power conversion efficiency of 25.48%due to their interfacial“adhesive”ability.Importantly,the stability of the NaPh-4PACz-based devices was significantly improved.展开更多
Minor self conjugate (msc) and skewpositive semidefinite (ssd) solutions to the system of matrix equations over skew fields [A mn X nn =A mn ,B sn X nn =O sn ] are considered. Necessary and su...Minor self conjugate (msc) and skewpositive semidefinite (ssd) solutions to the system of matrix equations over skew fields [A mn X nn =A mn ,B sn X nn =O sn ] are considered. Necessary and sufficient conditions for the existence of and the expressions for the msc solutions and the ssd solutions are obtained for the system.展开更多
The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by th...The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by the longstanding challenge of identifying sustainable membrane materials.In response,we propose a prototypal hybridization strategy to design a novel series of aminated conjugated microporous polymer(CMPN)@collagen fiber membrane(COLM).These sustainable and low-cost membrane materials allow a rapid and high-affinity kinetic to capture 90%of the uranium in just 30 min from 50 ppm with a high selectivity of Kd>105 mL·g^(−1).They also afford a robustly reusable adsorption capacity as high as 345 mg·g^(−1)that could harvest 1.61 mg·g^(−1)of uranium in a short 7-day real marine engineering in Fujian Province,even though suffered from very low uranium concentration of 3.29μg·L^(−1)and tough influence of salts such as 10.77 g·L^(−1)of Na^(+),1.75μg·L^(−1)of VO_(3)^(−)etc.in the rough seas.The structural evidence from both experimental and theoretical studies confirmed the formation of favorable chelating motifs from the amino group on CMPN-COLM,and the intensification by the synergistic effect from the size-sieving action of CMPN and the capillary inflow effect of COLM.展开更多
The development of multifunctional intelligent textiles has become an important innovation direction in the field of textile engineering, under the dual demands of intelligent health monitoring and environmental prote...The development of multifunctional intelligent textiles has become an important innovation direction in the field of textile engineering, under the dual demands of intelligent health monitoring and environmental protection. Although singlefunctional textiles with antibacterial, photochromic, and strain-sensing properties have been developed, they are unable to meet the demand for multifunctional textiles. In this respect, this study developed a poly(lactic acid) and poly(3-hydroxybutyrate)/thermoplastic polyurethane/carbon black nanoparticle composite nanofiber yarn(PPTCY) with a hollow-core-sheath structure using a simple conjugate electrospinning technology. PPTCY possessed excellent mechanical strength and could be effectively woven. More importantly, it not only enabled real-time visual monitoring of ultraviolet(UV) intensity in the environment but also possessed excellent antibacterial properties and strain-sensing performance. Its ΔE value was up to 58.24, and its antibacterial rates against Escherichia coli and Staphylococcus aureus were both 99.99%. This fabric had excellent strainsensing performance, high linearity, and durability under both pressure and stretching deformations. This research provides favorable technical support for the application of intelligent textiles in the field of UV protection and traffic safety.展开更多
Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection appl...Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection application.However,the presence of larger FA^(+)cation induces to an expansion of the Pb-I octahedral framework,which unfortunately affects both the stability and charge carrier mobility of the corresponding devices.To address this challenge,we develop a novel low-dimensional(HtrzT)PbI_(3) perovskite featuring a conjugated organic cation(1H-1,2,4-Triazole-3-thiol,HtrzT^(+))which matches well with theα-FAPbI_(3) lattices in two-dimensional plane.Benefiting from the matched lattice between(HtrzT)PbI_(3) andα-FAPbI_(3),the anchored lattice enhances the Pb-I bond strength and effectively mitigates the inherent tensile strain of theα-FAPbI_(3) crystal lattice.The X-ray detector based on(HtrzT)PbI_(3)(1.0)/FAPbI_(3) device achieves a remarkable sensitivity up to 1.83×10^(5)μC Gy_(air)^(−1) cm^(−2),along with a low detection limit of 27.6 nGy_(air) s^(−1),attributed to the release of residual stress,and the enhancement in carrier mobility-lifetime product.Furthermore,the detector exhibits outstanding stability under X-ray irradiation with tolerating doses equivalent to nearly 1.17×10^(6) chest imaging doses.展开更多
RNA interference has been widely used for gene therapy of various infectious diseases and malignant tumors. However, its poor stability in serum has limited further clinic application. Here, we found that stability of...RNA interference has been widely used for gene therapy of various infectious diseases and malignant tumors. However, its poor stability in serum has limited further clinic application. Here, we found that stability of siRNA in serum enhanced obviously when 3′-terminus of sense strand （siRNA-pS） was conjugated with peptide, while same conjugation at 3′-terminus of antisense strand brought no such effects. And it was also found that only the peptide residue in siRNA-pS could be cut off by RNase A. All these results indicated that nucleases in serum prefer to invade siRNA duplex through the 3′-end of sense strand.展开更多
Recent studies, focused on dihedral angles and intersection processes, have increased understandings of conjugate fault mechanisms. We present new 3-D seismic data and microstructural core analysis in a case study of ...Recent studies, focused on dihedral angles and intersection processes, have increased understandings of conjugate fault mechanisms. We present new 3-D seismic data and microstructural core analysis in a case study of a large conjugate strike-slip fault system from the intracratonic Tarim Basin, NW China. Within our study area, ＂X＂ type NE and NW trending faults occur within Cambrian- Ordovician carbonates. The dihedral angles of these conjugate faults have narrow ranges, 19~ to 62~ in the Cambrian and 26~ to 51~ in the Ordovician, and their modes are 42~ and 44~ respectively. These data are significantly different from the ~60~ predicted by the Coulomb fracture criterion. It is concluded that： （1） The dihedral angles of the conjugate faults were not controlled by confining pressure, which was low and associated with shallow burial; （2） As dihedral angles were not controlled by pressure they can be used to determine the shortening direction during faulting; （3） Sequential slip may have played an important role in forming conjugate fault intersections; （4） The conjugate fault system of the Tarim basin initiated as rhombic joints; these subsequently developed into sequentially active ＂X＂ type conjugate faults; followed by preferential development of the NW-trending faults; then reactivation of the NE trending faults. This intact rhombic conjugate fault system presents new insights into mechanisms of dihedral angle development, with particular relevance to intracratonic basins.展开更多
The initial cell search plays an important role during the process of downlink synchronization establishment between the User Equipment(UE) and the base station. In particular, the uncertainty of the synchronization s...The initial cell search plays an important role during the process of downlink synchronization establishment between the User Equipment(UE) and the base station. In particular, the uncertainty of the synchronization signals on the frequency domain and the flexibility of frame structure configuration have brought great challenges to the initial cell search for the fifth-generation(5G) new radio(NR). To solve this problem, firstly, we analyze the physical layer frame structure of 5G NR systems. Then, by focusing on the knowledge of synchronization signals, the 5G NR cell search process is designed, and the primary synchronization signal(PSS) timing synchronization algorithm is proposed, including a 5G-based coarse synchronization algorithm and conjugate symmetry-based fine synchronization algorithm. Finally, the performance of the proposed cell search algorithm in 5G NR systems is verified through the combination of Digital Signal Processing(DSP) and personal computer(PC). And the MATLAB simulation proves that the proposed algorithm has better performance than the conventional cross-correlation algorithm when a certain frequency offset exists.展开更多
BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated ...BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated systematically including review of history, physical examination for the stigmata of chronic liver disease, and other investigations. RESULT: Liver biopsy revealed a black liver with preserved architecture suggestive of DJS. CONCLUSIONS: SLE may develop in DJS. The relationship between DJS and SLE in this case is most likely a chance occurrence.展开更多
The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGA...The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.展开更多
A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chr...A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.31772213 and 31972320)the Excellent Youth Fund of Zhejiang Province,China(No.LR17C140002)
文摘An efficient genetic transformation system and suitable promoters are essential prerequisites for gene expression studies and genetic engineering in streptomycetes.In this study,firstly,a genetic transformation system based on intergeneric conjugation was developed in Streptomyces rimosus M527,a bacterial strain which exhibits strong antagonistic activity against a broad range of plant-pathogenic fungi.Some experimental parameters involved in this procedure were optimized,including the conjugative media,ratio of donor to recipient,heat shock temperature,and incubation time of mixed culture.Under the optimal conditions,a maximal conjugation frequency of 3.05^10-5 per recipie nt was obtai ned.Subseque ntly,based on the above developed and optimized tran sformati on system,the synthetic promoters SPL-21 and SPL-57,a native promoter potrB,and a constitutive promoter permE commonly used for gene expression in streptomycetes were selected and their activity was analyzed using gusA as a reporter gene in S.rimosus M527.Among the four tested promoters,SPL-21 exhibited the strongest expression activity and gave rise to a 2.2-fold increase in p-glucuronidase(GUS)activity compared with the control promoter permE.Promoter SPL-57 showed activity comparable to that of permE.Promoter potrB,which showed the lowest activity,showed a 50%decrease in GUS activity compared with the control permE.The transformation system developed in this study and the tested promotors provide a basis for the further modification of S.rimosus M527.
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
文摘In this paper, we consider 2 × 2 non-cooperative elliptic system involving Laplace operator defined on bounded, continuous and strictly Lipschitz domain of Rn. First we prove the existence and uniqueness for the state of the system under conjugation conditions;then we discuss the existence of the optimal control of boundary type with Neumann conditions, and we find the set of equations and inequalities that characterize it.
文摘The existence and uniqueness of the state for 2 × 2 Dirichlet cooperative elliptic systems under conjugation conditions are proved using Lax-Milgram lemma, then the boundary control for these systems is discussed. The set of equations and inequalities that characterizes this boundary control is found by theory of Lions, Sergienko and Deineka. The problem for cooperative Neumann elliptic systems under conjugation conditions is also considered. Finally, the problem for n × n cooperative elliptic systems under conjugation conditions is established.
基金financial supports from the Natural Science Foundation of Shandong Province(ZR2021ME037)the National Natural Science Foundation of China(52472259,22179051 and 61604143)+2 种基金the National Key Research and Development Program of China(2021YFE0111000)the Special Fund of Taishan Scholar Program of Shandong Province(tsqnz20221141)the Foundation of Key Laboratory of Advanced Technique&Preparation for Renewable Energy Materials,Ministry of Education,Yunnan Normal University(OF2022-02)。
文摘A comprehensive understanding of the relevance between molecular structure and passivation ability to screen efficient modifiers is essential for enhancing the performance of perovskite solar cells(PSCs).Here,three similarπ-πstacking molecules namely benzophenone(BPN),diphenyl sulfone(DPS),and diphenyl sulfoxide(DPSO)are used as back-interface modifiers in carbon-based CsPbBr_(3)PSCs.After investigation,the results demonstrate the positive effect of the p-πconjugation characteristic inπ-πstacking molecules on maximizing their passivation ability.The p-πco njugation of DPSO enables a higher coordinative activity of oxygen atom in its S=O group than that in 0=S=O group of DPS and C=O group of BPN,which gives a superior passivation effect of DPSO on defects of perovskite films.The modification of DPSO also significantly improves the p-type behavior of perovskite films and the back-interfacial energetics matching,inducing an increase of hole extraction and a decrease of energy loss.Finally,the unencapsulated carbon-based CsPbBr_(3)PSCs with DPSO achieve a maximum power conversion efficiency of 10.60%and outstanding long-term stability in high-temperature,high-humidity(85℃,85%relative humidity)air environment.This work provides insights into the influence of the structure ofπ-πstacking molecules on their ability to improve the perovskite films quality and therefore the PSCs performance.
文摘Organic luminescent materials hold significant promise for applications in modern technology.Traditionally,their design has been guided byπ-conjugation theory.However,the recent discovery of weak interactions-based luminescent materials,such as multiarylalkanes(MAAs),has challenged this paradigm.Emerging research suggests that these materials emit light from through-space conjugation(TSC),includingπ-π,n-π,and n-n TSC.Owing to their well-defined structures and facile chemical modification,MAAs serve as ideal models for investigating TSC.This review systematically examines the mechanisms of TSC in these systems from three key perspectives:conformational regulation,donor-acceptor(D-A)and n-electronic modulation.Studies on their photophysical processes reveal that conformational control and D-A electronic modulation predominantly influence emission throughπ-πTSC.In contrast,tuning the n-electron structure,particularly involving lone pair electrons on nitrogen atoms,introduces n-πand n-n TSC,enabling red-shifted emission and enhanced luminescence efficiency.By providing a comprehensive analysis of TSC in MAAs,this review refines the current understanding of TSC-based luminescence and offers valuable design principles for developing novel,highly efficient,weak interactions-based luminescent materials.
基金supported by the National Natural Science Foundation of China(Nos.22225806,22078314,21908216,22378385)Dalian Institute of Chemical Physics(Nos.DICPI202142,DICPI202436)+1 种基金Agency for Science,Technology and Research(No.A*STAR,Singapore)under its Advanced Manufacturing and Engineering Program(No.A2083c0051)SUTD Kickstarter Initiative(No.SKI 2021_03_10)。
文摘The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).
文摘After the third prezygotic division during conjugation of Paramecium caudatum,migratory and stationary pronuclei are produced.The migratory pronuclei remain in the paroral region tightly against the conjugating boundaries;while the stationary pronuclei are located beside the migratory pronuclei.To date,however,it is not clear what causes this close side-by-side localization between migratory and stationary pronuclei.In the current study,immunofluorescence staining with monoclonal antibody of anti-α tubulin indicated that ＂U＂ or ＂V＂ shaped spindles connected the migratory and stationary pronuclei during the third prezygotic division.This observation accounts for the close localization between these two types of pronuclei.
基金the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007)the open fund of National Key Laboratory of Advanced DrugFormulations for Overcoming Delivery Barriers(No.2024-KFB-003)+1 种基金the National Natural Science Foundation of China(No.82104109)Scientific Research Project of Liaoning Department of Education(No.LJ212410163045).
文摘Cancer is the second leading cause of death globally.Its treatment remains a major challenge due to the disease's complexity,heterogeneity,and adaptive nature.Among the array of available treatments,targeted therapy emerges as a paramount approach to address this substantial unmet clinical need,owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks.Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity,thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects.Therefore,as a burgeoning field in biomedical research,it is timely to outline the latest advances in drug conjugates-driven cancer treatment.Herein,we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands,linkers,payloads,and cancer treatments.This review focuses on several drug conjugates-related strategies,including antibody-drug conjugates(ADCs),peptide-drug conjugates(PDCs),small molecule-drug conjugates(SMDCs),aptamer-drug conjugates(ApDCs)and radionuclide-drug conjugates(RDCs).Finally,we discuss the fundamentals behind drug conjugate-based anticancer therapeutics,along with their inherent advantages and associated challenges,as well as recent research advances.
基金supported by the National Natural Science Foundation of China(61904053,22279033)the National Key Research and Development Program of China(2023YFB4204502)+2 种基金the 111 Project(B16016)the Fundamental Research Funds for the Central Universities(2025MS043)the Special Foundation for Carbon Peak Carbon Neutralization Technology Innovation Program of Jiangsu Province(BE2022026).
文摘Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended conjugation is designed and synthesized,named NaPh-4PACz.Compared to Ph-4PACz,NaPh-4PACz exhibits a larger adsorption energy with the ITO substrate,enabling the formation of a more uniform and dense film,thereby preventing direct contact between the perovskite and ITO.Additionally,NaPh-4PACz also has a stronger interaction with the perovskite,which can reduce buried interface defects and suppress non-radiative recombination.Consequently,NaPh-4PACz-based devices achieved a power conversion efficiency of 25.48%due to their interfacial“adhesive”ability.Importantly,the stability of the NaPh-4PACz-based devices was significantly improved.
文摘Minor self conjugate (msc) and skewpositive semidefinite (ssd) solutions to the system of matrix equations over skew fields [A mn X nn =A mn ,B sn X nn =O sn ] are considered. Necessary and sufficient conditions for the existence of and the expressions for the msc solutions and the ssd solutions are obtained for the system.
基金supported by National Natural Science Foundation of China(Grant No.22378066,22108040)Collaboration&Innovation Platform Project of National Independent Innovation Demonstration Zone(Fuzhou,Xiamen&Quanzhou)(Project No:3502ZCQXT2023004).
文摘The extraction of uranium from seawater via membrane adsorption is a promising strategy for ensuring a long-term supply of uranium and the sustainability of nuclear energy.However,this approach has been hindered by the longstanding challenge of identifying sustainable membrane materials.In response,we propose a prototypal hybridization strategy to design a novel series of aminated conjugated microporous polymer(CMPN)@collagen fiber membrane(COLM).These sustainable and low-cost membrane materials allow a rapid and high-affinity kinetic to capture 90%of the uranium in just 30 min from 50 ppm with a high selectivity of Kd>105 mL·g^(−1).They also afford a robustly reusable adsorption capacity as high as 345 mg·g^(−1)that could harvest 1.61 mg·g^(−1)of uranium in a short 7-day real marine engineering in Fujian Province,even though suffered from very low uranium concentration of 3.29μg·L^(−1)and tough influence of salts such as 10.77 g·L^(−1)of Na^(+),1.75μg·L^(−1)of VO_(3)^(−)etc.in the rough seas.The structural evidence from both experimental and theoretical studies confirmed the formation of favorable chelating motifs from the amino group on CMPN-COLM,and the intensification by the synergistic effect from the size-sieving action of CMPN and the capillary inflow effect of COLM.
基金supported by the Science and Technology Guidance Project of China National Textile and Apparel Council (Grant No.2024033)the Jiangsu Provincial Key Research and Development Program (Grant No.BE2019045)。
文摘The development of multifunctional intelligent textiles has become an important innovation direction in the field of textile engineering, under the dual demands of intelligent health monitoring and environmental protection. Although singlefunctional textiles with antibacterial, photochromic, and strain-sensing properties have been developed, they are unable to meet the demand for multifunctional textiles. In this respect, this study developed a poly(lactic acid) and poly(3-hydroxybutyrate)/thermoplastic polyurethane/carbon black nanoparticle composite nanofiber yarn(PPTCY) with a hollow-core-sheath structure using a simple conjugate electrospinning technology. PPTCY possessed excellent mechanical strength and could be effectively woven. More importantly, it not only enabled real-time visual monitoring of ultraviolet(UV) intensity in the environment but also possessed excellent antibacterial properties and strain-sensing performance. Its ΔE value was up to 58.24, and its antibacterial rates against Escherichia coli and Staphylococcus aureus were both 99.99%. This fabric had excellent strainsensing performance, high linearity, and durability under both pressure and stretching deformations. This research provides favorable technical support for the application of intelligent textiles in the field of UV protection and traffic safety.
基金supports from the National Natural Science Foundation of China(22375220,U2001214,22471302)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020101)Open Project Fund from State Key Laboratory of Optoelectronic Materials and Technologies(OEMT-2024-KF-08).
文摘Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection application.However,the presence of larger FA^(+)cation induces to an expansion of the Pb-I octahedral framework,which unfortunately affects both the stability and charge carrier mobility of the corresponding devices.To address this challenge,we develop a novel low-dimensional(HtrzT)PbI_(3) perovskite featuring a conjugated organic cation(1H-1,2,4-Triazole-3-thiol,HtrzT^(+))which matches well with theα-FAPbI_(3) lattices in two-dimensional plane.Benefiting from the matched lattice between(HtrzT)PbI_(3) andα-FAPbI_(3),the anchored lattice enhances the Pb-I bond strength and effectively mitigates the inherent tensile strain of theα-FAPbI_(3) crystal lattice.The X-ray detector based on(HtrzT)PbI_(3)(1.0)/FAPbI_(3) device achieves a remarkable sensitivity up to 1.83×10^(5)μC Gy_(air)^(−1) cm^(−2),along with a low detection limit of 27.6 nGy_(air) s^(−1),attributed to the release of residual stress,and the enhancement in carrier mobility-lifetime product.Furthermore,the detector exhibits outstanding stability under X-ray irradiation with tolerating doses equivalent to nearly 1.17×10^(6) chest imaging doses.
基金Ministry of Science and Technology of China(Grant No.2012CB720604)National Natural Science Foundation of China(Grant No.20932001)
文摘RNA interference has been widely used for gene therapy of various infectious diseases and malignant tumors. However, its poor stability in serum has limited further clinic application. Here, we found that stability of siRNA in serum enhanced obviously when 3′-terminus of sense strand （siRNA-pS） was conjugated with peptide, while same conjugation at 3′-terminus of antisense strand brought no such effects. And it was also found that only the peptide residue in siRNA-pS could be cut off by RNase A. All these results indicated that nucleases in serum prefer to invade siRNA duplex through the 3′-end of sense strand.
基金partly supportedby National Natural Science Foundation of China(Grant No.41472103)
文摘Recent studies, focused on dihedral angles and intersection processes, have increased understandings of conjugate fault mechanisms. We present new 3-D seismic data and microstructural core analysis in a case study of a large conjugate strike-slip fault system from the intracratonic Tarim Basin, NW China. Within our study area, ＂X＂ type NE and NW trending faults occur within Cambrian- Ordovician carbonates. The dihedral angles of these conjugate faults have narrow ranges, 19~ to 62~ in the Cambrian and 26~ to 51~ in the Ordovician, and their modes are 42~ and 44~ respectively. These data are significantly different from the ~60~ predicted by the Coulomb fracture criterion. It is concluded that： （1） The dihedral angles of the conjugate faults were not controlled by confining pressure, which was low and associated with shallow burial; （2） As dihedral angles were not controlled by pressure they can be used to determine the shortening direction during faulting; （3） Sequential slip may have played an important role in forming conjugate fault intersections; （4） The conjugate fault system of the Tarim basin initiated as rhombic joints; these subsequently developed into sequentially active ＂X＂ type conjugate faults; followed by preferential development of the NW-trending faults; then reactivation of the NE trending faults. This intact rhombic conjugate fault system presents new insights into mechanisms of dihedral angle development, with particular relevance to intracratonic basins.
基金partially the Chongqing Municipality’s Major Theme Project “R & D and Application of 5G terminal simulation equipment” (Grant No. Cstc2017zdcy-zdzx0030)
文摘The initial cell search plays an important role during the process of downlink synchronization establishment between the User Equipment(UE) and the base station. In particular, the uncertainty of the synchronization signals on the frequency domain and the flexibility of frame structure configuration have brought great challenges to the initial cell search for the fifth-generation(5G) new radio(NR). To solve this problem, firstly, we analyze the physical layer frame structure of 5G NR systems. Then, by focusing on the knowledge of synchronization signals, the 5G NR cell search process is designed, and the primary synchronization signal(PSS) timing synchronization algorithm is proposed, including a 5G-based coarse synchronization algorithm and conjugate symmetry-based fine synchronization algorithm. Finally, the performance of the proposed cell search algorithm in 5G NR systems is verified through the combination of Digital Signal Processing(DSP) and personal computer(PC). And the MATLAB simulation proves that the proposed algorithm has better performance than the conventional cross-correlation algorithm when a certain frequency offset exists.
文摘BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE). METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated systematically including review of history, physical examination for the stigmata of chronic liver disease, and other investigations. RESULT: Liver biopsy revealed a black liver with preserved architecture suggestive of DJS. CONCLUSIONS: SLE may develop in DJS. The relationship between DJS and SLE in this case is most likely a chance occurrence.
基金supported by the National Natural Science Foundation of China(No.81173006)Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.JKGQ201107)+1 种基金the Jiangsu Natural Science Foundation of China(No.BK20131312)the 12th of Six Talent Peak Foundation of Jiangsu Province
文摘The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.
基金supported by the Major National Scientific Research Projects (2015CB932103)
文摘A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.
